Endocrine Abstracts

Background: Hereditary hypophosphatemia (HH) are rare diseases, characterized by excessive renal phosphate wasting and inappropriately low 1,25-dihydroxy-vitamin D causing hypophosphatemia. In children, the disease manifests as rickets and osteomalacia, in adults osteomalacia. Complications from the disease appear with increasing age, in adults characterized by pain, arthrosis, persisting deformities of long bones if not corrected during childhood causing compromised functions...

Hypothyroidism and thyrotoxicosis have detrimental effects on skeletal development and adult bone strength. These effects result from thyroid hormone actions in bone, although a direct role for TSH in osteoblasts and osteoclasts was postulated following analysis of TSH receptor (TSHR) null mice. This hypothesis remains controversial as other studies failed to demonstrate osteoblast or osteoclast responses to TSH in vitro. Thyrostimulin is a heterodimeric glycoprotein ho...

Background: Lipocalin 2 (NGAL) is considered a pro-inflammatory adipokine. Noting the conflicting reports as to the role of Lipocalin 2 in metabolic disease, it remains unclear whether an acute or chronic state affects its impact on adipocyte function. In an attempt to address this our current studies investigated for the first time in humans, whether Lipocalin 2 in abdominal subcutaneous adipose tissue (AT) may influence mitochondrial function and browning of adipocytes, as c...

Background: In an obese state, pro-inflammatory adipokines can lead to mitochondrial dysfunction and reduced brown adipocytes properties in white adipocytes (BRITE adipocytes), all of which contribute to the pathogenesis of obesity and type 2 diabetes mellitus (T2DM). A recent novel adipokine, asprosin, that influences appetite and glucose homeostasis, appears to drive inflammation in obesity. However, asprosin expression in human adipose tissue (AT) depots, its impact on mito...

Background: Growth hormone insensitivity (GHI) is a continuum defined by normal/elevated growth hormone (GH), low IGF-I levels and growth restriction. Non-classical/mild-moderate GHI is poorly characterised and is frequently underdiagnosed. Heterozygous dominant negative (DN) gene variants located in the regions encoding the intracellular/transmembrane domains of the GH receptor cause a ‘non-classical’ GHI phenotype.Hypothesis/Objective: Detail...

The introduction of immune checkpoint inhibitors (ICIs) in clinical management of cancer has had an undeniable impact in management of cancer patients. Currently there are several ICIs are used across Europe including but not limited to, pembrolizumab, atezolizumab, and ipilimumab. Even though their clinical efficacy is reputable, they have the potential of causing serious immunotherapy-related adverse events’ (irADRs) in several organ systems including endocrine organs. ...

Case history: Two unrelated male patients were referred for evaluation of short stature. The first patient aged 16.5 years, had a birth weight of 2.6 kg at term (BWSDS -2.4), height 153 cm (HSDS -3.2) at referral and normal BMI SDS of 0.6. He had early postnatal hypoglycemia, which was conservatively managed, but no other significant clinical history. He had relative macrocephaly and disproportionate short stature. His mother was also short with a similar phenotype (height 147...

Background: Pathogenic IGFI gene mutations causing childhood growth failure are extremely rare. Only five autosomal recessive mutations, one IGFI copy number variant and two heterozygous frameshift mutations are reported. Heterozygous missense IGFI mutations haven’t previously been described.Objectives: To identify and functionally characterise a novel missense IGFI variant in a patient with postnatal growth failu...

Background: Asprosin is a novel adipokine involved in appetite and glucose regulation. During obesity, circulating asprosin is increased, which leads to increased inflammation and can disrupt cellular functions such as mitochondrial respiration. Asthma is a comorbidity of obesity, with both diseases sharing an inflammatory profile and mitochondrial dysfunction. This study investigated the molecular links between asthma and obesity, by exploring whether asprosin causes mitochon...

Background: The use of peptide receptor radionuclide therapy (PRRT) for neuroendocrine tumors (NETs) is increasing, but PRRT remains palliative at this time. Estrogen (E2) has been extensively linked to cellular proliferation and DNA repair in other cancers. Our aim is to determine whether NET cells are similarly affected by estrogen and whether inhibition of estrogen receptor alpha (ESR1) increases radiosensitivity of NET cells, which could improve PRRT response.<p class=...